Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence?
Background: Cenobamate (CNB) is an anti-seizure medication (ASM) approved in 2021 in Europe for adjunctive treatment of focal-onset seizures in adults who were not adequately controlled with at least two previous ASMs.Methods: seizure outcome, treatment-emergent adverse events, neuropsychological pr...
| Main Authors: | , , , , , , , , , , , , |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1239152/full |
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| author | Nicola Pietrafusa Giovanni Falcicchio Emilio Russo Simona Lattanzi Bianca Goffredo Raffaele Simeoli Sara Cairoli Tiziana Corsetti Roberta Roberti Marina De Tommaso Federico Vigevano Angela La Neve Nicola Specchio |
| author_facet | Nicola Pietrafusa Giovanni Falcicchio Emilio Russo Simona Lattanzi Bianca Goffredo Raffaele Simeoli Sara Cairoli Tiziana Corsetti Roberta Roberti Marina De Tommaso Federico Vigevano Angela La Neve Nicola Specchio |
| author_sort | Nicola Pietrafusa |
| collection | DOAJ |
| description | Background: Cenobamate (CNB) is an anti-seizure medication (ASM) approved in 2021 in Europe for adjunctive treatment of focal-onset seizures in adults who were not adequately controlled with at least two previous ASMs.Methods: seizure outcome, treatment-emergent adverse events, neuropsychological profile, and blood levels of CNB and concomitant ASM were analyzed in a real world setting in two different Italian epilepsy centers in the context of CNB early access program. All patients performed a general cognitive evaluation, while 32 patients underwent the administration of a battery of neuropsychological tests at baseline and 6 months after CNB treatment. We performed CNB quantification in plasma in 31 patients at different doses in the range of 100–400 mg/day (65 measures).Results: we enrolled 54 patients with a median age of 27.9 years. The mean follow-up was 10.7 months. Most (91%) completed the efficacy analysis. At last follow-up visit, a 69.5% median seizure reduction was registered. Thirty-two patients (59.2%) had a ≥50% reduction of seizures that was ≥75% in 20 (42.0%) cases, whilst 10 (20.2%) patients were seizure-free. The most common adverse events were somnolence (53.1%), dizziness (28.1%) and diplopia (12.5%). The correlation between CNB dose and plasma concentration, revealed a significant linear correlation (r = 0.86, p < 0.0001), and there was a significant difference in mean plasma concentration/dose administered ratio (C/D ratio) between patients taking or not at least one inducer (0.10 ± 0.04 [(μg/mL)/(mg/day)]; n = 47 vs. 0.13 ± 0.05 [(μg/mL)/(mg/day)]; n = 18, p = 0.04). CNB dose was inversely correlated (r = −0.31, p = 0.02) to the C/D ratio of Carbamazepine blood levels. and positively correlated (r = 0.74, p < 0.0001) with an increased plasma concentration of the active Clobazam metabolite N-desmethylclobazam. General Anxiety Disorder-7 showed a significant improvement of score from baseline evaluation of 6.82 to follow-up 6 months evaluation of 4.53 (p = 0.03).Conclusion: In this real-world study, we registered a clinically meaningful reduction in seizure frequency after CNB administration in most patients along with a good tolerability profile. CNB treatment is correlate to a reduction in symptom severity of anxiety score. Plasma levels measurements confirm that CNB acts both as “victim” and as “perpetrator” of drug-drug interactions. |
| first_indexed | 2024-03-08T21:33:22Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T21:33:22Z |
| publishDate | 2023-12-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-9c5993e6d1dd47cba23648716cd6dd482023-12-21T04:46:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-12-011410.3389/fphar.2023.12391521239152Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence?Nicola Pietrafusa0Giovanni Falcicchio1Emilio Russo2Simona Lattanzi3Bianca Goffredo4Raffaele Simeoli5Sara Cairoli6Tiziana Corsetti7Roberta Roberti8Marina De Tommaso9Federico Vigevano10Angela La Neve11Nicola Specchio12Clinical and Experimental Neurology, Full Member of European Reference Network EpiCARE, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Translational Biomedicine and Neurosciences, University of Bari ‘Aldo Moro’, Bari, ItalyScience of Health Department, University Magna Grecia of Catanzaro, Catanzaro, ItalyNeurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, ItalyDivision of Metabolic Diseases and Drug Biology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDivision of Metabolic Diseases and Drug Biology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDivision of Metabolic Diseases and Drug Biology, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyHospital Pharmacy Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyScience of Health Department, University Magna Grecia of Catanzaro, Catanzaro, ItalyDepartment of Translational Biomedicine and Neurosciences, University of Bari ‘Aldo Moro’, Bari, ItalyHead of Neurological Sciences and Rehabilitation Medicine Scientific Area, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Translational Biomedicine and Neurosciences, University of Bari ‘Aldo Moro’, Bari, ItalyClinical and Experimental Neurology, Full Member of European Reference Network EpiCARE, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyBackground: Cenobamate (CNB) is an anti-seizure medication (ASM) approved in 2021 in Europe for adjunctive treatment of focal-onset seizures in adults who were not adequately controlled with at least two previous ASMs.Methods: seizure outcome, treatment-emergent adverse events, neuropsychological profile, and blood levels of CNB and concomitant ASM were analyzed in a real world setting in two different Italian epilepsy centers in the context of CNB early access program. All patients performed a general cognitive evaluation, while 32 patients underwent the administration of a battery of neuropsychological tests at baseline and 6 months after CNB treatment. We performed CNB quantification in plasma in 31 patients at different doses in the range of 100–400 mg/day (65 measures).Results: we enrolled 54 patients with a median age of 27.9 years. The mean follow-up was 10.7 months. Most (91%) completed the efficacy analysis. At last follow-up visit, a 69.5% median seizure reduction was registered. Thirty-two patients (59.2%) had a ≥50% reduction of seizures that was ≥75% in 20 (42.0%) cases, whilst 10 (20.2%) patients were seizure-free. The most common adverse events were somnolence (53.1%), dizziness (28.1%) and diplopia (12.5%). The correlation between CNB dose and plasma concentration, revealed a significant linear correlation (r = 0.86, p < 0.0001), and there was a significant difference in mean plasma concentration/dose administered ratio (C/D ratio) between patients taking or not at least one inducer (0.10 ± 0.04 [(μg/mL)/(mg/day)]; n = 47 vs. 0.13 ± 0.05 [(μg/mL)/(mg/day)]; n = 18, p = 0.04). CNB dose was inversely correlated (r = −0.31, p = 0.02) to the C/D ratio of Carbamazepine blood levels. and positively correlated (r = 0.74, p < 0.0001) with an increased plasma concentration of the active Clobazam metabolite N-desmethylclobazam. General Anxiety Disorder-7 showed a significant improvement of score from baseline evaluation of 6.82 to follow-up 6 months evaluation of 4.53 (p = 0.03).Conclusion: In this real-world study, we registered a clinically meaningful reduction in seizure frequency after CNB administration in most patients along with a good tolerability profile. CNB treatment is correlate to a reduction in symptom severity of anxiety score. Plasma levels measurements confirm that CNB acts both as “victim” and as “perpetrator” of drug-drug interactions.https://www.frontiersin.org/articles/10.3389/fphar.2023.1239152/fullcenobamateepilepsyfocal-onset seizuresdrug-resistanceblood levelsneuropsychology |
| spellingShingle | Nicola Pietrafusa Giovanni Falcicchio Emilio Russo Simona Lattanzi Bianca Goffredo Raffaele Simeoli Sara Cairoli Tiziana Corsetti Roberta Roberti Marina De Tommaso Federico Vigevano Angela La Neve Nicola Specchio Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence? Frontiers in Pharmacology cenobamate epilepsy focal-onset seizures drug-resistance blood levels neuropsychology |
| title | Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence? |
| title_full | Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence? |
| title_fullStr | Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence? |
| title_full_unstemmed | Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence? |
| title_short | Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence? |
| title_sort | cenobamate as add on therapy for drug resistant epilepsies effectiveness drug to drug interactions and neuropsychological impact what have we learned from real word evidence |
| topic | cenobamate epilepsy focal-onset seizures drug-resistance blood levels neuropsychology |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1239152/full |
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